Modulating endothelial adhesion and migration impacts stem cell therapies efficacy.

Autor:	Schäfer R; Institute for Transfusion Medicine and Immunohematology, German Red Cross Blood Donor Service Baden-Württemberg-Hessen gGmbH, Goethe-University Hospital, Frankfurt am Main, Germany; Institute of Clinical and Experimental Transfusion Medicine, University Hospital Tübingen, Tübingen, Germany. Electronic address: richard.schaefer.md@gmail.com., Schwab M; Department of Clinical Pharmacology, University Hospital Tübingen, Tübingen, Germany; Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany; Department of Pharmacy and Biochemistry, University of Tübingen, Tübingen, Germany; Neuroscience Laboratory and Departments of Biochemistry and Clinical Pharmacology, Yerevan State Medical University, Yerevan, Armenia., Siegel G; Institute of Clinical and Experimental Transfusion Medicine, University Hospital Tübingen, Tübingen, Germany., von Ameln-Mayerhofer A; Department of Pharmacy, Sindelfingen-Böblingen Medical Center, University of Tübingen, Sindelfingen, Germany., Buadze M; Department of Clinical Pharmacology, University Hospital Tübingen, Tübingen, Germany., Lourhmati A; Department of Clinical Pharmacology, University Hospital Tübingen, Tübingen, Germany., Wendel HP; Departments of Thoracic, Cardiac and Vascular Surgery, University Hospital Tübingen, Tübingen, Germany., Kluba T; Departments of Orthopaedic Surgery, University Hospital Tübingen, Tübingen, Germany., Krueger MA; Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, University Hospital Tübingen, Tübingen, Germany., Calaminus C; Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, University Hospital Tübingen, Tübingen, Germany., Scheer E; Institute of Clinical and Experimental Transfusion Medicine, University Hospital Tübingen, Tübingen, Germany., Dominici M; Department of Medical and Surgical Sciences for Children & Adults, University Hospital of Modena and Reggio Emilia, Modena, Italy., Grisendi G; Department of Medical and Surgical Sciences for Children & Adults, University Hospital of Modena and Reggio Emilia, Modena, Italy., Doeppner TR; Department of Neurology, University of Duisburg-Essen, Essen, Germany; Department of Neurology, University Medical Center Göttingen, Göttingen, Germany., Schlechter J; Department of Neurology, University of Duisburg-Essen, Essen, Germany., Finzel AK; Department of Clinical Pharmacology, University Hospital Tübingen, Tübingen, Germany., Gross D; Department of Clinical Pharmacology, University Hospital Tübingen, Tübingen, Germany., Klaffschenkel R; Institute of Clinical and Experimental Transfusion Medicine, University Hospital Tübingen, Tübingen, Germany., Gehring FK; Institute of Clinical and Experimental Transfusion Medicine, University Hospital Tübingen, Tübingen, Germany; 3T GmbH & Co. KG, Tuttlingen, Germany., Spohn G; Institute for Transfusion Medicine and Immunohematology, German Red Cross Blood Donor Service Baden-Württemberg-Hessen gGmbH, Goethe-University Hospital, Frankfurt am Main, Germany., Kretschmer A; Institute for Transfusion Medicine and Immunohematology, German Red Cross Blood Donor Service Baden-Württemberg-Hessen gGmbH, Goethe-University Hospital, Frankfurt am Main, Germany., Bieback K; Institute of Transfusion Medicine and Immunology, German Red Cross Blood Service Baden-Württemberg - Hessen gGmbH, Medical Faculty Mannheim, Heidelberg University, Germany., Krämer-Albers EM; Institute for Developmental Biology and Neurobiology, Johannes Gutenberg University Mainz, Mainz, Germany., Barth K; Institute for Developmental Biology and Neurobiology, Johannes Gutenberg University Mainz, Mainz, Germany., Eckert A; Neurobiology Laboratory for Brain Aging and Mental Health, Molecular and Cognitive Neuroscience, University of Basel, Basel, Switzerland., Elser S; Department of Radiology, University Hospital Tübingen, Tübingen, Germany., Schmehl J; Department of Radiology, University Hospital Tübingen, Tübingen, Germany., Claussen CD; Department of Radiology, University Hospital Tübingen, Tübingen, Germany., Seifried E; Institute for Transfusion Medicine and Immunohematology, German Red Cross Blood Donor Service Baden-Württemberg-Hessen gGmbH, Goethe-University Hospital, Frankfurt am Main, Germany., Hermann DM; Department of Neurology, University of Duisburg-Essen, Essen, Germany., Northoff H; Institute of Clinical and Experimental Transfusion Medicine, University Hospital Tübingen, Tübingen, Germany., Danielyan L; Department of Clinical Pharmacology, University Hospital Tübingen, Tübingen, Germany; Department of Pharmacy and Biochemistry, University of Tübingen, Tübingen, Germany. Electronic address: lusine.danielyan@med.uni-tuebingen.de.
Jazyk:	angličtina
Zdroj:	EBioMedicine [EBioMedicine] 2020 Oct; Vol. 60, pp. 102987. Date of Electronic Publication: 2020 Sep 14.
DOI:	10.1016/j.ebiom.2020.102987
Abstrakt:	Background: Limited knowledge of stem cell therapies` mechanisms of action hampers their sustainable implementation into the clinic. Specifically, the interactions of transplanted stem cells with the host vasculature and its implications for their therapeutic efficacy are not elucidated. We tested whether adhesion receptors and chemokine receptors on stem cells can be functionally modulated, and consequently if such modulation may substantially affect therapeutically relevant stem cell interactions with the host endothelium. Methods: We investigated the effects of cationic molecule polyethylenimine (PEI) treatment with or without nanoparticles on the functions of adhesion receptors and chemokine receptors of human bone marrow-derived Mesenchymal Stem Cells (MSC). Analyses included MSC functions in vitro, as well as homing and therapeutic efficacy in rodent models of central nervous system´s pathologies in vivo. Findings: PEI treatment did not affect viability, immunomodulation or differentiation potential of MSC, but increased the CCR4 expression and functionally blocked their adhesion receptors, thus decreasing their adhesion capacity in vitro. Intravenously applied in a rat model of brain injury, the homing rate of PEI-MSC in the brain was highly increased with decreased numbers of adherent PEI-MSC in the lung vasculature. Moreover, in comparison to untreated MSC, PEI-MSC featured increased tumour directed migration in a mouse glioblastoma model, and superior therapeutic efficacy in a murine model of stroke. Interpretation: Balanced stem cell adhesion and migration in different parts of the vasculature and tissues together with the local microenvironment impacts their therapeutic efficacy. Funding: Robert Bosch Stiftung, IZEPHA grant, EU grant 7 FP Health. Competing Interests: Declaration of Competing Interest Dr. Danielyan reports grants from IZEPHA, during the conduct of the study. Dr. Schwab reports grants from Robert Bosch Stiftung (Stuttgart, Germany) during the conduct of the study. Dr. Schäfer reports a grant from the Commission of the European Communities during the conduct of the study. Dres Schäfer, Danielyan, von Ameln-Mayerhofer, Wendel, Kluba, Dominici, Claussen, Northoff and Siegel have a patent DE102012111891.4.; EP13801557.3. Dr. Gehring is a shareholder of 3T analytic. All other authors have no competing interests. (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze:	MEDLINE
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